Formulation for menopausal women

ABSTRACT

The present disclosure relates to novel compositions which provide improved nutritional support for premenopausal and menopausal women and/or relief from symptoms associated with menopause, as well as prophylactic effects, and methods for using same.

This application is a divisional application of U.S. Pat. applicationSer. No. 09/409,059, filed Sep. 30, 1999, now U.S. Pat. No. 6,479.545the entire contents of which is hereby incorporated by reference in itsentirety.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention is directed to novel compositions for use bypremenopausal women and menopausal women for the purpose of providingimproved nutritional support and/or relief from the symptoms ofmenopause, as well as to methods for using same.

2. Description of the Related Art

Menopause, the transition from the reproductive stage to thenon-reproductive stage of a woman's life, is characterized primarily bythe cessation of menstruation. However, menopause has come to signifymuch more than simply the loss of reproductive capability, as it is alsoassociated with a number of acute and chronic conditions. Menopausalsyndrome consists of a number of varying and often highly distressingsymptoms resulting from hormonal imbalance and nutritional deficiency inthe female body.

Hot flashes and sweating secondary to vasomotor instability affect 75%of women. Psychologic and emotional symptoms of fatigue, insomnia,irritability and nervousness are common. Lack of sleep due todisturbance by recurring hot flashes contributes to fatigue andirritability. Dizziness, parenthesis and cardiac symptoms ofpalpitations and tachycardia may also occur; the incidence of heartdisease increases. Other common symptoms include nausea, constipation,diarrhea, arthralgia and myalgia. The Merck Manual, 1793 (16^(th) Ed.1992).

Menopause is also characterized by osteoporosis, or loss of bonedensity, resulting in increased bone fractures and vertebral columncollapse. Bone loss begins around age 35. This loss accelerates duringmenopause, which generally occurs around age 45 to 55. Bone mass lossesaverage 1-2% each year after menopause. Primary sites are the vertebrae,which show anterior collapse resulting in stooping and backache, thehips and the wrist. The Merck Manual 1793(16^(th) Ed. 1992).Osteoporosis develops over decades and is related to peak bone mass, aswell as to the degree of bone loss.

Estrogen replacement therapy has been used to relieve the symptoms ofmenopause. The Merck Manual 1793(16^(th) Ed. 1992). However, estrogentherapy is not without its limitations. In some instances the sideeffects of estrogen therapy can be quite severe. These side effectsinclude increased risk of certain cancers, such as breast cancer.Estrogen has also been implicated in certain endometrial cancers.Although treatments with progestin have been shown to counter theseadverse side effects, postmenopausal women treated with such anestrogen-progestin regimen frequently experience undesirable uterinebleeding. Further, hormone therapy alone is insufficient to meet thevaried and heightened nutritional requirements of a woman during thisphase in her life. Adequate nutritional intake is also necessary.

Appropriate nutritional intake is increasingly important to menopausalwomen. For example, adequate calcium intake prevents osteoporosis.Moreover, certain vitamins and minerals enhance calcium absorption andutilization. However, while vitamin and mineral supplements providingcalcium for women is known in the art, conventional supplements fail tomeet other nutritional requirements of menopausal women. Specifically,conventional supplements lack certain fatty acids which are especiallyuseful to treat symptoms of fatigue or tiredness commonly experienced bya woman undergoing menopause. Fatty acids are essential in supportinglife's activities as the body derives most of its energy fromtriglycerides, a molecule of glycerol with three fatty acids. Linoleicacid and linolenic acid, in particular, are two fatty acids which areindispensable to body functions. The inclusion of these two fatty acidsin nutritional supplements is of particular significance because theyare not produced by the body and must be supplied through food. However,conventional nutritional supplements fail to include these two fattyacids.

The use of fatty acids in various forms and for various purposes hasbeen previously disclosed. Horrobin et al. disclose a method ofprevention or treatment of endometriosis wherein effective amounts ofone or both gamma-linolenic acid and/or dihomo-gamma-linolenic acid areadministered to women. Specifically, the fatty acids may be administeredin the form of the acid itself or as an ester, amide, salt or any otherfunctional derivative capable of being converted to the acid within thebody and may be from natural or synthetic sources.

Maxson et al., U.S. Pat. No. 4,900,734, disclose a pharmaceuticalcomposition containing estradiol and progesterone for oraladministration. Specifically, the pharmaceutical composition comprisesestradiol dissolved in an oil vehicle containing a suspension ofmicronized progesterone. Further, the oil vehicle is high in glyceridesof polyunsaturated fatty acids. Specifically, linoleic and linolenicacids are disclosed as particularly effective polyunsaturated fattyacids. The combined administration of these steroids is disclosed asbeing useful for replacement hormone therapy in the treatment ofmenopausal women.

Cohen, U.S. Pat. No. 4,945,103, discloses a method for treating womenwho suffer from premenstrual syndrome (PMS) which comprisesadministration of melatonin in sufficient doses to relieve symptomsassociated with PMS. Specifically, Cohen discloses that progestogen canbe administered in combination with melatonin. Further, melatonin can beadministered to women orally, parenterally or in the form of an implant.Cohen specifically discloses that PMS may be linked to a nutritionaldeficiency in either vitamin B-complex, especially vitamin B6(pyroxidine), or essential fatty acids, especially linolenic acid.

Horrobin, U.S. Pat. No. 5,380,757, discloses a method of treatment ofvulvar dystrophy and/or vaginal dryness, which medicament comprisesgamma-linolenic (GIA) and/or dihomo-gamma-linolenic acid (DGIA),optionally in association with other essential fatty acids of the n-6 orn-3 series. Horrobin discloses that deficiency of linoleic acid in thediet may produce atrophy and hyperkeratosis of the skin.

Miyamoto et al., U.S. Pat. No. 5,461,170, disclose a glyceridepreparation having a branched saturated fatty acid and/or myristic acidresidues for use in liquid oils and/or solid cosmetics of the same.Specifically, Miyamoto et al. disclose a polyol fatty-acid ester havingmixed acid group produced by reacting a partial ester of a polyol and abranched fatty acid with a straight chain fatty acid or a lower alcoholester thereof in the presence of a lipase. The obtained glyceridemixture contains a large amount of diglyceride having a branched,saturated fatty acid group and a straight chain, fatty acid group. Thereference does not specifically disclose either linoleic or linolenicacid and/or menopause.

Sultenfuss, U.S. Pat. No. 5,514,382, discloses a daily vitamin andmineral supplement for women comprising vitamin A, beta-carotene,niacin, riboflavin, pantothenic acid, pyridoxine, cyanocobalamin,biotin, paraaminobenzoic acid, inositol, choline, calcium, chromium,copper, iodine, iron, magnesium, manganese, molybdenum, selenium, zinc,and bioflavonoid. For women over 40 years of age, iron is optionallyincluded.

Shylankevich, U.S. Pat. No. 5,569,459, discloses compositions containingvarious vitamins, minerals and herbal extracts that can be used foralleviation of premenstrual syndrome, menopausal disorders, andstimulating estrogen production. Specifically, the invention relates tosuch pharmaceutical compositions and dietary supplements that containnatural soybean phytoestrogens of the isoflavone group.

Vitamins For Women disclose a Calcium/Vitamin/Mineral supplement programfor women over forty. Specifically, the “over forty” formula discloses acomposition containing ingredients which come in day and/or nightformulas that “assure better utilization and absorption.” Physicians'sDesk Reference for Nonprescription Drugs, (9^(th) Ed., 1988) 718.

However, the previously disclosed formulations are deficient for variousreasons. In particular, none of the previously disclosed formulationscontain critical components, such as essential fatty acids or calcium,in amounts specifically tailored to meet the needs of premenopausal andmenopausal women. Moreover, the previously disclosed formulations failto disclose the significance of the proportion of the various componentsto one another. Therefore, there is a need for formulations specificallytailored to meet the needs of menopausal women. Further, there is a needfor drug delivery regimens which are specifically adapted to meet theneeds of premenopausal and menopausal women.

SUMMARY OF THE INVENTION

The compositions of the present inventive subject matter overcome thedeficiencies of currently-available nutritional supplements by providingformulations and drug delivery regimens which are specifically tailoredfor women just prior to, during and after the period of menopause. Thepresent compositions contain a novel combination of various components,such as fatty acids, in critical ratios and amounts, optionally incombination with various vitamins and minerals.

One embodiment of the present inventive subject matter is a compositionfor administration to a menopausal woman, which comprises:

an essential fatty acid compound selected from the group consisting of alinoleic acid compound, a linolenic acid compound, a docosahexaenoicacid compound, an omega-3 fatty acid compound, an omega-2 fatty acidcompound, a derivative thereof and a combination thereof in an amount ofabout 10 mg to about 1,000 mg;

a calcium compound or derivative thereof in an amount of about 400 mg toabout 2500 mg;

a folic acid compound or derivative thereof in an amount of about 0.4 mgto about 5.0 mg; and

wherein the weight ratio of the essential fatty acid compound to thecalcium compound or derivative thereof is about 1:0.4 to 250 in a singleor multiple dosage unit.

Another embodiment of the present inventive subject matter is acomposition for administration to a menopausal woman, which comprises:

a first fatty acid compound selected from the group consisting of alinoleic acid compound, a derivative thereof and a combination thereofin an amount of about 10 mg to about 1,000 mg;

a second fatty acid compound selected from the group consisting of alinolenic acid compound, a derivative thereof and combinations thereofin an amount of about 10 mg to about 1,000 mg;

a third fatty acid compound selected from the group consisting of adocosahexaenoic acid compound, an omega-3 fatty acid, an omega-2 fattyacid, a derivative thereof and a combination thereof in an amount ofabout 10 mg to about 1,000 mg;

a calcium compound or derivative thereof in an amount of about 400 mg toabout 2500 mg;

a folic acid compound or derivative thereof in an amount of about 0.4 mgto about 5.0 mg;

wherein the weight ratio of the sum of the amounts of said first andsecond fatty acid compounds to the amount of said third fatty acidcompound is about 1:0.5 to 1.5; and

wherein the weight ratio of the sum of the amounts of said first, secondand third fatty acid compounds to the amount of said calcium compound orderivative thereof is about 1:0.4 to 50.

A further embodiment of the present inventive subject matter is acomposition for administration to a menopausal woman, which comprises:

a first fatty acid compound selected from the group consisting of alinoleic acid compound, a derivative thereof and a combination thereofin an amount of about 10 mg to about 1,000 mg;

a second fatty acid compound selected from the group consisting of alinolenic acid compound, a derivative thereof and combinations thereofin an amount of about 10 mg to about 1,000 mg;

a third fatty acid compound selected from the group consisting of adocosahexaenoic acid compound, an omega-3 fatty acid, an omega-2 fattyacid, a derivative thereof and a combination thereof in an amount ofabout 10 mg to about 1,000 mg;

a calcium compound or derivative thereof in an amount of about 400 mg toabout 2500 mg;

a folic acid compound or derivative thereof in an amount of about 0.4 mgto about 5.0 mg;

a vitamin C compound or derivative thereof in an amount of about 25 mgto about 500 mg;

a vitamin E compound or derivative thereof in an amount of about 10 mgto about 500 mg;

wherein the weight ratio of the sum of the amounts of said first andsecond fatty acid compounds to the amount of said third fatty acidcompound is about 1:0.5 to 1.5; and

wherein the weight ratio of the sum of the amounts of said first, secondand third fatty acid compounds to the amount of said calcium compound orderivative thereof is about 1:0.4 to 50.

An even further embodiment of the present inventive subject matter is acomposition for administration to a menopausal woman, which comprises:

a first fatty acid compound selected from the group consisting of alinoleic acid compound, a derivative thereof and a combination thereofin an amount of about 10 mg to about 1,000 mg;

a second fatty acid compound selected from the group consisting of alinolenic acid compound, a derivative thereof and combinations thereofin an amount of about 10 mg to about 1,000 mg;

a third fatty acid compound selected from the group consisting of adocosahexaenoic acid compound, an omega-3 fatty acid, an omega-2 fattyacid, a derivative thereof and a combination thereof in an amount ofabout 10 mg to about 1,000 mg;

a calcium compound or derivative thereof in an amount of about 400 mg toabout 2500 mg;

a folic acid compound or derivative thereof in an amount of about 0.4 mgto about 5.0 mg;

a vitamin C compound or derivative thereof in an amount of about 25 mgto about 500 mg;

a vitamin E compound or derivative thereof in an amount of about 10 mgto about 500 mg;

a vitamin A compound or derivative thereof in an amount of about 2,500IU to about 6,500 IU;

wherein the weight ratio of the sum of the amounts of said first andsecond fatty acid compounds to the amount of said third fatty acidcompound is about 1:0.5 to1.5; and

wherein the weight ratio of the sum of said first, second and thirdfatty acid compounds to the amount of said calcium compound orderivative thereof is about 1:0.4 to 50.

Another embodiment of the present inventive subject matter is acomposition for administration to a menopausal woman, which comprises:

a first fatty acid compound selected from the group consisting of alinoleic acid compound, a derivative thereof and a combination thereofin an amount of about 10 mg to about 1,000 mg;

a second fatty acid compound selected from the group consisting of alinolenic acid compound, a derivative thereof and combinations thereofin an amount of about 10 mg to about 1,000 mg;

a third fatty acid compound selected from the group consisting of adocosahexaenoic acid compound, an omega-3 fatty acid, an omega-2 fattyacid, a derivative thereof and a combination thereof in an amount ofabout 10 mg to about 1,000 mg;

a calcium compound or derivative thereof in an amount of about 400 mg toabout 2500 mg;

a folic acid compound or derivative thereof in an amount of about 0.4 mgto about 5.0 mg;

a vitamin C compound or ester derivative thereof in an amount of about25 mg to about 500 mg;

a vitamin E compound or derivative thereof in an amount of about 10 mgto about 500 mg;

a vitamin B6 compound or derivative thereof in an amount of about 10 mgto about 50 mg;

a vitamin B12 compound or derivative thereof in an amount of about 25mcg to about 75 mcg;

a vitamin D compound or derivative thereof in an amount of about 200 IUto about 625 IU;

wherein the weight ratio of the sum of the amounts of said first andsecond fatty acid compounds to the amount of said third fatty acidcompound is about 1:0.5 to 1.5; and

wherein the weight ratio of the sum of the amounts of said first, secondand third fatty acid compounds to the amount of said calcium compound orderivative thereof is about 1:0.4 to 50.

Yet another embodiment of the present inventive subject matter is acomposition for administration to a menopausal woman, which comprises:

a biologically active substance for treating symptoms of menopause;

a calcium compound or derivative thereof in an amount of about 400 mg toabout 2500 mg;

a folic acid compound or derivative thereof in an amount of about 0.4 mgto about 5.0 mg.

A further embodiment of the present inventive subject matter is a drugdelivery regimen, which comprises:

a first dosage form comprising a first biologically active substance tobe administered to a menopausal woman at a predetermined time period;

a second dosage form comprising a second biologically active substanceto be administered to the menopausal woman simultaneously with saidfirst dosage form;

wherein said first biologically active substance and said secondbiologically active substance are incompatible substances.

An additional embodiment of the present inventive subject matter is amethod for providing nutritional supplementation to a menopausal woman,which comprises:

administering an essential fatty acid compound to the woman during theperiod commencing at the onset of menopause, said essential fatty acidcompound being selected from the group consisting of a linoleic acidcompound, a linolenic acid compound, a docosahexaenoic acid compound, anomega-3 fatty acid compound, an omega-2 fatty acid compound, aderivative thereof and a combination thereof;

administering about 400 mg to about 2500 mg of a calcium compound orderivative thereof to the woman during the period commencing at theonset of menopause; administering about 0.4 mg to about 5.0 mg of afolic acid compound or derivative thereof to the woman during the periodcommencing at the onset of menopause; and

wherein the weight ratio of the essential fatty acid compound to thecalcium compound or derivative thereof is about 1:0.4 to 250.

Another embodiment of the present inventive subject matter is a methodfor providing nutritional supplementation to a menopausal woman, whichcomprises:

administering a first fatty acid compound to the woman during a periodcommencing at the onset of menopause, said first fatty acid compoundbeing selected from the group consisting of a linoleic acid compound, aderivative thereof and a combination thereof;

administering a second fatty acid compound to said woman during theperiod commencing at the onset of menopause, said second fatty acidcompound being selected from the group consisting of a linolenic acidcompound, a derivative thereof and a combination thereof;

administering a third fatty acid compound to said woman during theperiod commencing at the onset of menopause, said third fatty acidcompound being selected from the group consisting of a docosahexaenoicacid compound, an omega-3 fatty acid, an omega-2 fatty acid, aderivative thereof and a combination thereof, and said third fatty acidcompound being provided to the woman together with said first and secondfatty acid compounds;

administering about 400 mg to about 2500 mg of a calcium compound orderivative thereof to said woman;

wherein the weight ratio of the sum of the amounts of said first andsecond fatty acid compounds to the amount of said third fatty acidcompound is about 1:0.5 to 1.5; and

wherein the weight ratio of the sum of the amounts of said first, secondand third fatty acid compound to the amount of said calcium compound orderivative thereof is about 1:0.4 to 50.

Yet another embodiment of the present inventive subject matter is amethod for providing nutritional supplementation to a menopausal womanwhile reducing symptoms associated with menopause, which comprises:

administering a first fatty acid compound to the woman during a periodcommencing at the onset of menopause, said first fatty acid compoundbeing selected from the group consisting of a linoleic acid compound, aderivative thereof and a combination thereof;

administering a second fatty acid compound to said woman during theperiod commencing at the onset of menopause, said second fatty acidcompound being selected from the group consisting of a linolenic acidcompound, a derivative thereof and a combination thereof;

administering a third fatty acid compound to said woman during theperiod commencing at the onset of menopause, said third fatty acidcompound being selected from the group consisting of a docosahexaenoicacid compound, an omega-3 fatty acid, an omega-2 fatty acid, aderivative thereof and a combination thereof, and said third fatty acidcompound being provided to the woman together with said first and secondfatty acid compounds;

administering about 400 mg to 2500 mg of a calcium compound orderivative thereof to said woman;

administering a therapeutic substance to said woman;

wherein the weight ratio of the sum of the amounts of said first andsecond fatty acid compounds to the amount of said third fatty acidcompound is about 1:0.5 to 1.5; and

wherein the weight ratio of the sum of said first, second and thirdfatty acid compound to the amount of said calcium compound or derivativethereof is about 1:0.4 to 50.

A further embodiment is a method for delaying the onset of menopause,which comprises: administering an essential fatty acid to a woman priorto menopause, said fatty acid being selected from the group consistingof a linoleic acid compound, a linolenic acid compound, adocosahexaenoic acid compound, an omega-3 fatty acid compound, anomega-2 fatty acid compound, a derivative thereof and a combinationthereof; wherein said essential fatty acid is administered in an amountsufficient to delay the onset of menopause.

A still further embodiment is a method for providing nutritionalsupplementation to a menopausal woman while reducing symptoms associatedwith menopause, which comprises:

administering a fatty acid compound to the woman during a periodcommencing at the onset of menopause, said fatty acid compound beingselected from the group consisting of a linoleic acid compound, alinolenic acid compound, a docosahexaenoic acid compound, an omega-3fatty acid, an omega-2 fatty acid, a derivative thereof and acombination thereof;

administering about 400 mg to 2500 mg of a calcium compound orderivative thereof to said woman;

and administering a non-nutritional active to said woman.

Another embodiment is a method for reducing the possibility of prematuremenopause, which comprises: administering an essential fatty acid to awoman prior to menopause, said fatty acid being selected from the groupconsisting of a linoleic acid compound, a linolenic acid compound, adocosahexaenoic acid compound, an omega-3 fatty acid compound, anomega-2 fatty acid compound, a derivative thereof and a combinationthereof; wherein said essential fatty acid is administered in an amountsufficient to reduce the risk of premature menopause.

An additional embodiment is a method for providing nutritionalsupplementation to a premenopausal woman or a menopausal woman, whichcomprises: administering to the premenopausal woman or menopausal womana biologically active substance for treating symptoms of menopause;administering to the premenopausal woman or menopausal woman a calciumcompound or derivative thereof in an amount of 400 mg to about 2500; andadministering to the premenopausal woman or menopausal woman a folicacid compound or derivative thereof in an amount of about 0.4 mg toabout 5.0 mg.

DETAILED DESCRIPTION OF THE INVENTION

As used herein, “menopausal woman” refers to any woman who hasexperienced ovarian failure. The ovarian failure can be measured byblood tests for low estrogen levels (estradiol) or elevated gonadotropinlevels (follicle stimulating hormone). When menopause occurs it remainsfor the life of the woman. The term “menopause” also encompasses thepostmenopause or the postmenopausal period. The term “menopause” alsoencompasses natural menopause and artificial menopause.

“Premenopausal woman” refers to any woman during the period commencingfive years prior to onset of menopause.

“Nutritional stores” refers to the levels of vitamins, minerals andother nutrients which will be available for use by the menopausal woman.

“Nutritional status” refers to the presence or absence of any nutrientdeficiency, or in other words, the extent to which physiologicalnutrient demands are being satisfied such that deficiency is avoided.

“Optimize neurological development” refers to attainment of the highestdegree of neurological development possible through natural processeswithout the use of any unnatural substances or procedures, such asdrugs, surgery and the like.

“Biologically active substance” refers to any substance or substancescomprising a drug, active therapeutic substance, metabolite, medicament,vitamin, or mineral, any substance used for treatment, prevention,diagnosis, cure or mitigation of disease or illness, any substance whichaffects anatomical structure or physiological function, or any substancewhich alters the impact of external influences on an animal, ormetabolite thereof, and as used herein, encompasses the terms “activesubstance”, “therapeutic substance”, “agent”, “active agent”, “drug”,“medication”, “medicine”, “medicant”, and other such similar terms.

“Non-nutritional active” refers to any substance or substancescomprising a drug, active therapeutic substance, metabolite, ormedicament, or any other substance used for treatment, prevention,diagnosis, cure or mitigation of disease or illness, any substance whichaffects anatomical structure or physiological function, or any substancewhich alters the impact of external influences on an animal, ormetabolite thereof, and as used herein, that is not a vitamin, mineral,or any other nutritional compound or compositions.

“Specific physiological needs” refers to the unique requirements forcertain levels of certain nutrients by one class of persons, such asmenopausal women, premenopausal women, postmenopausal women, etc., asdistinguished from other classes.

“Biologically-acceptable” refers to being safe for human consumption.

“Storage-incompatible substances” refers to substances that may not beformulated together in a single dosage unit or stored together in directcontact because the substances will interact in a negative manner andalso substances that cannot be formulated together in a single dosageunit because the sum total of the dosage amounts of the substances wouldresult in a single dosage unit which is too large to be swallowed. Theterm also refers to substances which may be stored in direct contact,however, one of the substances is preferably formulated in a dosage formwhich is either not preferred or incompatible with the other substance.Storage-incompatibility also refers to two or more substances wherein atleast one substance is a prescription substance and at least onesubstance is a non-prescription substance.

“Storage-incompatibility” refers to the state that exists betweenstorage-incompatible substances, as defined above.

The compositions of the present inventive subject matter provide severalspecific new and unexpected benefits. First, the formulations ensurethat menopausal women are provided with adequate energy during theperiod of menopause. Secondly, the formulations allow the menopausalwomen to maintain adequate fatty acid stores for both her future use.Thirdly, the fatty acids optimize the neurological maintenance of themenopausal women. Fourthly, when administered just prior to menopause,the present compositions prepare women for the increased physiologicaldemands and stresses to be placed upon their bodies. Additionally, thepresent compositions provide nutritional supplementation to women duringthe early stage of menopause known as perimenopause. Finally, thepresent compositions help minimize the risk of menopause relateddisorders and symptoms resulting from such disorders.

The present inventive subject matter is based, in part, on the discoverythat when compositions having certain fatty acids, in certain amountsand proportions to one another, are administered to women just prior to,during and after menopause, the women will achieve optimal nutritionalsupplementation. In particular, supplementing a menopausal woman's dietwith the formulations described below for a period commencing whensymptoms of menopause are actually experienced, or preferably just priorto when menopause would generally be expected, will ensure that thewoman has adequate essential fatty acids for present and future use. Thefatty acid supplement may also further contain vitamins and minerals toconfer added health benefits to the menopausal woman. In addition tobenefitting humans, the present invention can also benefit non-humanmammals. The composition of the present invention could be administeredto a mammal in animal feed, pill form, or other appropriate dosage formsto such mammals.

Without being limited by theory, the present compositions stimulate orplay a vital role in one or more natural biological pathways. Forexample, the arachidonic acid cascade may play a significant role in thesupport and maintenance of a menopausal woman's health. Specifically, inthe arachidonic acid cascade, linoleic acid is converted first togamma-linolenic acid and then to further metabolites such asdihomo-gamma-linolenic acid and arachidonic acid which are precursors of1 and 2 series prostaglandin respectively, as shown in the outlinebelow:

The present composition may contain an essential fatty acid compound.The fatty acid compound may be a linoleic acid compound, derivativesthereof or any combination of linoleic acid and/or linoleic acidderivatives. The fatty acid compound may be a linolenic acid compound,derivatives thereof and/or an combinations of linolenic acid and/orlinoleic acid derivatives. The fatty acid compound may also be adocosahexaenoic acid compound, an omega-3 fatty acid compound, anomega-2 fatty acid compound, derivatives thereof or combinationsthereof. The fatty acid may further be a combination of any of the abovediscussed fatty acids.

Preferably, the fatty acid compound is present in the composition in anamount ranging from about 10 mg to 1,000 mg. More preferably, the fattyacid compound is present in the composition in an amount ranging fromabout 15 mg to 200 mg, independently of the other fatty acid compounds.Even more preferably, the fatty acid compounds is present in thecomposition in an amount ranging from about 20 mg to about 100 mg,independently of the other fatty acid compounds. Most preferably, thefatty acid compound is present in the composition in an amount rangingfrom about 25 mg to 50 mg, independently of the other fatty acidcompounds.

Three fatty acid compounds may be present in the present composition incritical proportions to one another. Preferably, the weight ratio of thesum of the amounts of said first and second fatty acid compounds to theamount of said third fatty acid compound is about 1:0.5 to 1.5. Morepreferably, the weight ratio of the sum of the amounts of said first andsecond fatty acid compounds to the amount of said third fatty acidcompound is about 1:0.7 to 1.3. Even more preferably, the weight ratioof the sum of the amounts of said first and second fatty acid compoundsto the amount of said third fatty acid compound is about 1:0.9 to 1.2.Most preferably, the weight ratio of the sum of the amounts of saidfirst and second fatty acid compounds to the amount of said third fattyacid compound is about 1:0.9 to 1.1.

The compositions of the present invention may incorporate any compoundthat can react with an essential fatty acid to form a biochemicallyactive compound. Preferably, the compound is a compound which fulfills anutritional need, for example, without limitation, sphingomyelin,myelin, derivatives thereof and combinations thereof.

Particular classes of fatty acid compound derivatives used in thepresent invention, include, without limitation, phospholipid esters oflinoleic acid, ethers of linoleic acid, sterolderivatives of linoleicacid, phospholipid esters of linolenic acid, ethers of linolenic acid,sterolderivatives of linolenic acid and combinations thereof.

Non-limiting exemplary fatty acid compounds used in the presentinvention, include, without limitation, phosphatidal choline esters oflinoleic acid, phosphatidal ether of linoleic acid, sipolsterol ester oflinoleic acid, phosphatidal choline esters of linolenic acid,phosphatidal ether of linolenic acid, sipolsterol ester of linolenicacid and combinations thereof.

The present composition contains a calcium compound, derivatives thereofor any combination of calcium compound and derivatives thereof.Preferably, the calcium is present in the composition in an amountranging from about 400 mg to about 2,500 mg. More preferably, thecalcium is present in the composition in an amount ranging from about600 mg to about 1,800 mg. Even more preferably, the calcium is presentin the composition in an amount ranging from about 800 mg to about 1600mg. Most preferably, the calcium is present in the composition in anamount ranging from about 1,000 mg to about 1400 mg.

The proportion of total fatty acids to total calcium content in thepresent inventions is a critical feature.

Where three fatty acid compounds are present, preferably, the weightratio of the sum of the amounts of the first, second and third fattyacid compounds to the amount of said calcium compound or derivativethereof is about 1:0.4 to 50. More preferably, the weight ratio of thesum of the amounts of the first, second and third fatty acid compoundsto the amount of said calcium compound or derivative thereof is about1:4 to 20. Even more preferably, the weight ratio of the sum of theamounts of the first, second and third fatty acid compounds to theamount of said calcium compound or derivative thereof is about 1:7 to15. Most preferably, the weight ratio of the sum of the amounts of thefirst, second and third fatty acid compounds to the amount of saidcalcium compound or derivative thereof is about 1:10 to 14.

The fatty acids of the present inventive subject matter may be used assuch or as biologically acceptable and physiologically equivalentderivatives as, for example, detailed later herein. Reference to any ofthe fatty acids including reference in the claims is to be taken asincluding reference to the acids when in the form of such derivatives.Equivalence is demonstrated by entry into the biosynthetic pathways ofthe body as evidenced by effects corresponding to those of the acidsthemselves or their natural glyceride esters. Thus, indirectidentification of useful derivatives is by their having the valuableeffect in the body of the fatty acid itself, but conversion, forexample, of gamma-linolenic acid to dihomo-gamma-linolenic acid and onto arachidonic acid can be shown directly by gas chromatographicanalysis of concentrations in blood, body fat, or other tissue bystandard techniques, well known to persons of ordinary skill in the artto which the present inventive subject matter pertains.

Derivatives of linoleic acid, as used in the present inventive subjectmatter, include, without limitation, salts of linoleic acid, alkalinesalts of linoleic acid, esters of linoleic acid and combinationsthereof. Derivatives of linolenic acid, as used in the present inventivesubject matter, include, without limitation, salts of linolenic acid,alkaline salts of linolenic acid, esters of linolenic acid andcombinations thereof. The salts and alkaline salts herein refer to thoseregularly used organic or inorganic salts which are acceptable forpharmaceutical use. Non-limiting exemplary linolenic acids includegamma-linoleic acid and dihomo-gamma-linolenic acid.

The fatty acids of the present inventive subject matter may be from anysource, including, without limitation, natural or synthetic oils, fats,waxes or combinations thereof. Moreover, the fatty acids herein may bederived, without limitation, from non-hydrogenated oils, partiallyhydrogenated oils, fully hydrogenated oils or combinations thereof.Non-limiting exemplary sources of fatty acids include seed oil, fish ormarine oil, canola oil, vegetable oil, safflower oil, sunflower oil,nasturtium seed oil, mustard seed oil, olive oil, sesame oil, soybeanoil, corn oil, peanut oil, cottonseed oil, rice bran oil, babassu nutoil, palm oil, low erucic rapeseed oil, palm kernel oil, lupin oil,coconut oil, flaxseed oil, evening primrose oil, jojoba, tallow, beeftallow, butter, chicken fat, lard, dairy butterfat, shea butter orcombinations thereof. Specific non-limiting exemplary fish or marine oilsources include shellfish oil, tuna oil, mackerel oil, salmon oil,menhaden, anchovy, herring, trout, sardines or combinations thereof.Preferably, the source of the fatty acids is fish or marine oil, soybeanoil or flaxseed oil.

Calcium compounds include, but are not limited to, any of the well knowncalcium supplements, such as calcium carbonate, calcium sulfate, calciumoxide, calcium hydroxide, calcium apatite, calcium citrate-malate, bonemeal, oyster shell, calcium gluconate, calcium lactate, calciumphosphate, calcium levulinate, and the like. Derivatives of calciumcompounds, as used herein, include, without limitation, salts ofcalcium, alkaline salts of calcium, esters of calcium, and combinationsthereof. The salts and alkaline salts herein refer to those regularlyused organic or inorganic salts which are acceptable for pharmaceuticaluse. The calcium of the present composition may be from any source,without limitation.

Folic acid is also incorporated into the composition of the presentinventive subject matter. Preferably, folic acid is present in an amountranging from about 0.4 mg to about 5.0 mg. More preferably, folic acidis present in an amount ranging from about 0.6 mg to about 1.3 mg. Evenmore preferably, folic acid is present in an amount ranging from about0.8 mg to about 1.2 mg. Most preferably, folic acid is present in anamount ranging from about 0.9 mg to about 1.1 mg.

The present composition may optionally contain additional vitamins andbiologically-acceptable minerals. Non-limiting exemplary vitamins andbiologically acceptable minerals and their derivatives thereof forinclusion in the present compositions include vitamin A, B vitamins,vitamin C, vitamin D, vitamin E, vitamin K, iron, calcium, magnesium,potassium, copper, chromium, zinc, molybdenum, iodine, boron, selenium,manganese, bioflavonoid, derivatives thereof or combinations thereof.These vitamins and minerals may be from any source or combination ofsources, without limitation. Non-limiting exemplary B vitamins include,without limitation, thiamine, niacinamide, pyridoxine, riboflavin,cyanocobalamin, biotin, pantothenic acid or combinations thereof. Othernutritionally active compounds may also be present, including withoutlimitation, fiber, carbohydrates, fats, proteins, amino acids,derivatives thereof and combinations thereof.

When vitamin C is present in the composition of the present inventivesubject matter, it is preferably present in an amount ranging from about10 mg to about 600 mg. More preferably, the vitamin C is present in anamount ranging from about 25 mg to about 500 mg. Even more preferably,the vitamin C is present in an immediate release form in an amountranging from about 25 mg to about 50 mg. Most preferably, the vitamin Cis present in a controlled release form in an amount ranging from about250 mg to about 500 mg.

When vitamin E is present in the composition of the present inventivesubject matter, it is preferably present in an amount ranging from about5 mg to about 500 mg. More preferably, the vitamin E is present in anamount ranging from about 10 mg to about 400 mg. Even more preferably,the vitamin E is present in a controlled release form in an amountranging from about 250 mg to about 400 mg. Most preferably, the vitaminE is present in an immediate release form in an amount ranging fromabout 10 mg to about 50 mg.

Vitamin B6 may also be present in the composition of the presentinventive subject matter. Vitamin B6 is preferably present in an amountranging from about 5 mg to about 200 mg. More preferably, vitamin B6 ispresent in an amount ranging from about 10 mg to about 50 mg. Even morepreferably, vitamin B6 is present in an amount ranging from 15 mg toabout 40 mg. Most preferably, vitamin B6 is present in a controlledrelease form in an amount ranging from 20 mg to about 30 mg.

Vitamin B12 may also be incorporated into the present composition.Preferably, the vitamin B12 is present in an amount ranging from about25 mcg to about 75 mcg. More preferably, the vitamin B12 is present inan amount ranging from about 35 mcg to about 65 mcg. Even morepreferably, the vitamin B12 is present in an amount ranging from about40 mcg to about 60 mcg. Most preferably, the vitamin B12 is present inan amount ranging from about 45 mcg to about 55 mcg.

Vitamin D may also be incorporated into the present composition.Preferably, vitamin D is present in an amount ranging from about 200 IUto about 625 IU. More preferably, vitamin D is present in an amountranging from about 300 IU to about 500 IU. Even more preferably, vitaminD is present in an amount ranging from about 350 IU to about 450 IU.Most preferably, vitamin D is present in an amount ranging from about375 IU to about 425 IU.

Vitamin A may also be incorporated into the present composition.Preferably, vitamin A is present in the composition in an amount rangingfrom about 2,500 IU to about 6,500 IU. More preferably, vitamin A ispresent in the composition in an amount ranging from about 4,000 IU toabout 6,000 IU. Even more preferably, vitamin A is present in thecomposition in an amount ranging from about 4,500 IU to about 5,500 IU.Most preferably, vitamin A is present in the composition in an amountranging from about 4,750 IU to about 5,250 IU.

Magnesium, when present, is preferably in the composition of the presentinventive subject matter in an amount ranging from about 25 mg to about400 mg. More preferably, magnesium is present in the composition of thepresent inventive subject matter in an immediate release form in anamount ranging from about 25 mg to about 100 mg. Even more preferably,magnesium is present in the composition of the present inventive subjectmatter in a controlled release form in an amount ranging from about 100mg to about 400 mg. Acceptable magnesium compounds which may beincorporated into the present inventive subject matter include, but arenot limited to, magnesium stearate, magnesium carbonate, magnesiumoxide, magnesium hydroxide and magnesium sulfate.

The composition of the present inventive subject matter may also includeone or more biologically active substances or therapeutic substances,including, without limitation, hormones, steroids, fiber, estrogens,progestins, sedative-hypnotics, barbiturates, benzodiazepines,antidepressants, tranquilizers, sedatives, osteoporotics,anti-platelets, aminobisphosphonates, herbals, herbal derivatives, plantderivatives, phyto-chemical derivatives and combinations thereof.

If the non-nutritional active is a hormone, the hormone is administeredin a dosage amount ranging from about 0.15 mg to about 11.25 mg. If thenon-nutritional active is an osteoporotic, the osteoporotic isadministered in a dosage amount ranging from about 2.5 mg to about 60mg.

Non-limiting exemplary therapeutic substances include,medroxyprogesterone acetate, megestrol acetate, clonidine, norethindroneacetate, ethinyl estradiol, conjugated estrogen, natural estrogen,synthetic estrogen, estradiol, progesterone, clomiphene, clomiphenecitrate, zuclomiphene, zuclomiphene citrate, enclomiphene, enclomiphenecitrate, aspirin, calcitonin, alendronate, etidronate, pamidronate,clodronate, tiludronate, residronate, ibandronate and combinationsthereof.

Non-limiting exemplary herbals and herbal derivatives include agrimony,alfalfa, aloe vera, amaranth, angelica, anise, barberry, basil,bayberry, bee pollen, birch, bistort, blackberry, black cohosh, blackwalnut, blessed thistle, blue cohosh, blue vervain, boneset, borage,buchu, buckthorn, bugleweed, burdock, capsicum, cayenne, caraway,cascara sagrada, catnip, celery, centaury, chamomile, chaparral,chickweed, chicory, chinchona, cloves, coltsfoot, comfrey, cornsilk,couch grass, cramp bark, culver's root, cyani, cornflower, damiana,dandelion, devils claw, dong quai, echinacea, elecampane, ephedra,eucalyptus, evening primrose, eyebright, false unicorn, fennel,fenugreek, figwort, flaxseed, garlic, gentian, ginger, ginseng, goldenseal, gotu kola, gum weed, hawthorn, hops, horehound, horseradish,horsetail, hoshouwu, hydrangea, hyssop, iceland moss, irish moss,jojoba, juniper, kelp, lady's slipper, lemon grass, licorice, lobelia,mandrake, marigold, marjoram, marshmallow, mistletoe, mullein, mustard,myrrh, nettle, oatstraw, oregon grape, papaya, parsley, passion flower,peach, pennyroyal, peppermint, periwinkle, plantain, pleurisy root,pokeweed, prickly ash, psyllium, quassia, queen of the meadow, redclover, red raspberry, redmond clay, rhubarb, rose hips, rosemary, rue,safflower, saffron, sage, St. Johnswort, sarsaparilla, sassafras, sawpalmetto, scullcap, senega, senna, shepherd's purse, slippery elm,spearmint, spikenard, squawvine, stillingia, strawberry, taheebo, thyme,uva ursi, valerian, violet, watercress, white oak bark, white pine bark,wild cherry, wild lettuce, wild yam, willow, wintergreen, witch hazel,wood betony, wormwood, yarrow, yellow dock, yerba santa, yucca andcombinations thereof. Herbal derivatives, as used herein, refers toherbal extracts, and substances derived from plants and plant parts,such as leaves, flowers and roots, without limitation. Preferably, theherbal or herbal derivative is black cohosh, licorice, false unicorn,siberian ginseng, sarsaparilla, squaw vine, blessed thistle andcombinations thereof.

Various additives may be incorporated into the present composition.Optional additives of the present composition include, withoutlimitation, starches, sugars, fats, antioxidants, amino acids, proteins,nucleic acids, electrolytes, derivatives thereof or combinationsthereof.

Non-limiting exemplary amino acids of the present inventive subjectmatter include histidine, isoleucine, leucine, lysine, methionine,phenylalanine, threonine, tryptophan, valine, alanine, arginine,asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine,proline, serine, tyrosine, derivatives thereof, and combinationsthereof. Preferably, the amino acid present is leucine, isoleucine,valine, derivatives thereof or combinations thereof.

The compositions, methods and drug delivery regimens of the presentinventive subject matter may facilitate the simultaneous administrationof storage-incompatible substances, particularly storage incompatiblesubstances tailored to the needs of premenopausal and menopausal women.Storage-incompatible substances may be any substances that may not beformulated together in a single dosage unit or stored together in directcontact because the substances will interact in a negative manner andalso substances that cannot be formulated together in a single dosageunit because the sum total of the dosage amounts of the substances wouldresult in a single dosage unit which is too large to be swallowed.Storage-incompatible substances also include those substances which maybe stored in direct contact, however, one of the substances ispreferably formulated in a dosage form which is either not preferred orincompatible with the other substance. The storage-incompatiblesubstances may include any storage-incompatible substances, withoutlimitation.

For example, the storage incompatible substances may be hydrophobiccompounds and hydrophilic compounds, olefinic compounds and non-olefiniccompounds, pH sensitive compounds and non-pH sensitive compounds,substances requiring an anhydrous environment and substances requiring anon-anhydrous environment, acidic drugs and basic drugs, effervescenttablets and high water content drugs or dosage forms, gelatin capsulesand aldehydes, quaternary ammonium compounds and anionic substances orany combination of the above.

Storage incompatible substances also include substances that cannot beformulated together in a single dosage unit because the sum total of thedosage amounts of the substances results in a single dosage unit toolarge to swallow. The compositions, methods and drug delivery regimensof the present inventive subject matter address this problem byseparating the large dosage into multiple doses small enough to swallowcomfortably, while keeping all of the substances and doses together inone package.

Non-limiting exemplary storage incompatible substances include, withoutlimitation, ascorbic acid and aluminum hydroxide, ascorbic acid andsodium bicarbonate, citric acid and sodium carbonate, folic acid andcalcium carbonate, activated charcoal and amyl nitrate, gelatin capsulesand formaldehyde, gelatine capsules and gluteraldehyde, konicin chlorideand soap, etylpyridinium chloride and sodium stearate, omega fatty acidsand combinations thereof.

It is also possible in the nutritional composition of the presentinventive subject matter for the dosage form to combine any forms ofrelease well known to persons of ordinary skill in the art. Theseinclude, without limitation, immediate release, extended release, pulserelease, variable release, controlled release, timed release, sustainedrelease, delayed release, long acting, and combinations thereof. Theability to obtain immediate release, extended release, pulse release,variable release, controlled release, timed release, sustained release,delayed release, long acting characteristics and combinations thereof isperformed using well known procedures and techniques available to theordinary artisan. Each of these specific techniques or procedures forobtaining the release characteristics does not constitute an inventiveaspect of this inventive subject matter all of which procedures are wellknown to those of ordinary skill in the art. As used herein, a“controlled release form” means any form having at least one componentformulated for controlled release. As used herein, “immediate releaseform” means any form having all its components formulated for immediaterelease.

Any biologically-acceptable dosage form well known to persons ofordinary skill in the art, and combinations thereof, are contemplated bythe inventive subject matter. Examples of such dosage forms include,without limitation, chewable tablets, quick dissolve tablets,effervescent tablets, reconstitutable powders, elixirs, liquids,solutions, suspensions, emulsions, tablets, multi-layer tablets,bi-layer tablets, capsules, soft gelatin capsules, hard gelatincapsules, caplets, lozenges, chewable lozenges, beads, powders,granules, particles, microparticles, dispersible granules, cachets,douches, suppositories, creams, topicals, inhalants, aerosol inhalants,patches, particle inhalants, implants, depot implants, ingestibles,injectables, infusions, health bars, confections, animal feeds, cereals,yogurts, cereal coatings, foods, nutritive foods, functional foods andcombinations thereof. The preparation of the above dosage forms are wellknown to persons of ordinary skill in the art.

The following procedures represent, without limitation, acceptablemethods of preparing formulations falling within the scope of theinventive subject matter. For example, animal feed may be made bymethods well known to persons of ordinary skill in the art. Animal feedsmay be prepared by mixing the formulation with binding ingredients toform a plastic mass. The mass is then extruded under high pressure toform tubular (or “spaghetti-like”) structures that are cut to pelletsize and dried.

Quick dissolve tablets may be prepared, for example, without limitation,by mixing the formulation with agents such as sugars and cellulosederivatives, which promote dissolution or disintegration of theresultant tablet after oral administration, usually within 30 seconds.

Cereal coatings may be prepared, for example, without limitation, bypassing the cereal formulation, after it has been formed into pellets,flakes, or other geometric shapes, under a precision spray coatingdevice to deposit a film of active ingredients, plus excipients onto thesurface of the formed elements. The units thus treated are then dried toform a cereal coating.

For example, health bars may be prepared, without limitation, by mixingthe formulation plus excipients (e.g., binders, fillers, flavors,colors, etc.) to a plastic mass consistency. The mass is then eitherextended or molded to form “candy bar” shapes that are then dried orallowed to solidify to form the final product.

Soft gel or soft gelatin capsules may be prepared, for example, withoutlimitation, by dispersing the formulation in an appropriate vehicle(vegetable oils are commonly used) to form a high viscosity mixture.This mixture is then encapsulated with a gelatin based film usingtechnology and machinery known to those in the soft gel industry. Theindustrial units so formed are then dried to constant weight.

Chewable tablets, for example, without limitation, may be prepared bymixing the formulations with excipients designed to form a relativelysoft, flavored, tablet dosage form that is intended to be chewed ratherthan swallowed. Conventional tablet machinery and procedures, that isboth direct compression and granulation, i.e., or slugging, beforecompression, can be utilized. Those individuals involved inpharmaceutical solid dosage form production are well versed in theprocesses and the machinery used as the chewable dosage form is a verycommon dosage form in the pharmaceutical industry.

Film coated tablets, for example, without limitation, may be prepared bycoating tablets using techniques such as rotating pan coating methods orair suspension methods to deposit a contiguous film layer on a tablet.This procedure is often done to improve the aesthetic appearance oftablets, but may also be done to improve the swallowing of tablets, orto mask an obnoxious odor or taste, or to improve the usual propertiesof an unsightly uncoated tablet.

Compressed tablets, for example, without limitation, may be prepared bymixing the formulation with excipients intended to add binding qualitiesto disintegration qualities. The mixture is either directly compressedor granulated then compressed using methods and machinery quite wellknown to those in the industry. The resultant compressed tablet dosageunits are then packaged according to market need, i.e., unit dose,rolls, bulk bottles, blister packs, etc.

The present inventive subject matter contemplates nutritionalcompositions formulated for administration by any route, includingwithout limitation, oral, buccal, sublingual, rectal, parenteral,topical, inhalational, injectable and transdermal. The physicochemicalproperties of nutritional compositions, their formulations, and theroutes of administration are important in absorption. Absorption refersto the process of nutritional composition movement from the site ofadministration toward the systemic circulation. Most orally administerednutritional compositions are in the form of tablets or capsulesprimarily for convenience, economy, stability, and patient acceptance.They must disintegrate and dissolve before absorption can occur. Usingthe present inventive subject matter with any of the above routes ofadministration or dosage forms is performed using well known proceduresand techniques available to the ordinary skilled artisan.

The present inventive subject matter contemplates the use ofbiologically-acceptable carriers which may be prepared from a wide rangeof materials. Without being limited thereto, such materials includediluents, binders and adhesives, lubricants, plasticizers,disintegrants, colorants, bulking substances, flavorings, sweeteners andmiscellaneous materials such as buffers and adsorbents in order toprepare a particular medicated composition.

Binders may be selected from a wide range of materials such ashydroxypropylmethylcellulose, ethylcellulose, or other suitablecellulose derivatives, povidone, acrylic and methacrylic acidco-polymers, pharmaceutical glaze, gums, milk derivatives, such as whey,starches, and derivatives, as well as other conventional binders wellknown to persons skilled in the art. Exemplary non-limiting solvents arewater, ethanol, isopropyl alcohol, methylene chloride or mixtures andcombinations thereof. Exemplary non-limiting bulking substances includesugar, lactose, gelatin, starch, and silicon dioxide.

The plasticizers used in the dissolution modifying system are preferablypreviously dissolved in an organic solvent and added in solution form.Preferred plasticizers may be selected from the group consisting ofdiethyl phthalate, diethyl sebacate, triethyl citrate, cronotic acid,propylene glycol, butyl phthalate, dibutyl sebacate, caster oil andmixtures thereof, without limitation. As is evident, the plasticizersmay be hydrophobic as well as hydrophilic in nature. Water-insolublehydrophobic substances, such as diethyl phthalate, diethyl sebacate andcaster oil are used to delay the release of water-soluble vitamins, suchas vitamin B6 and vitamin C. In contrast, hydrophilic plasticizers areused when water-insoluble vitamins are employed which aid in dissolvingthe encapsulated film, making channels in the surface, which aid innutritional composition release.

The composition of the present inventive subject matter may beadministered in a partial, i.e., fractional dose, one or more timesduring a 24 hour period, a single dose during a 24 hour period of time,than a double dose during a 24 hour period of time, or more an a doubledose during a 24 hour period of time. Fractional, double or othermultiple doses may be taken simultaneously or at different times duringthe 24 hour period. The doses may be uneven doses with regard to oneanother or with regard to the individual components at differentadministration times. For example, without limitation, the amount ofcalcium in a morning dose is different from the amount of calcium in anevening dose.

The compositions of the present invention are intended for use by humansand other mammals. The dosages are adjusted according to body weight andthus may be set forth herein on a per body weight basis. For example, ifthe formula specifies a range of about 10-1000 mg for a 55 kgindividual, that range would be adjusted for a 35 kg individual to about6.3-63 mg (e.g., the lower range limit=(35 kg/55 kg)*10 mg=6.3 mg).Decimal amounts may be rounded to the nearest whole number. In the abovemanner the present compositions may thus be adapted to be suitable forany individual, including any mammal, regardless of its size.

The present composition is adapted to meet the specific physiologicalneeds of a menopausal woman. For example, the formulations may focus onspecial nutritional needs of a menopausal woman that are not generallyor adequately addressed in nutritional or dietary supplements, such asessential fatty acids, without limitation. The iron and calcium, whenpresent, are provided in amounts to optimize nutritional benefit to themenopausal woman, while minimizing unpleasant side effects which mayaccompany overly large doses. The formulation can be further tailoredbased upon the specific needs, genetic predispositions or identifieddeficiencies of individual women, on either a generalized or case bycase basis for greater specificity. Further, the composition may bespecifically adapted for treating conditions associated with menopauseor to maximize neurological maintenance of a menopausal woman. Thecomposition may also be adapted for inhibiting loss in bone mass andpreventing deficiency of essential fatty acids in menopausal women.Moreover, the present composition can be used as one component of aprescribed therapy.

The compositions of the inventive subject matter may be provided in ablister pack or other such pharmaceutical package, without limitation.Further, the compositions of the present inventive subject matter mayfurther include or be accompanied by indicia allowing women to identifythe compositions as products for menopausal women. The indicia mayfurther additionally include an indication of the above specified timeperiods for using said compositions. For example, without limitation,the indicia may be time indicia indicating a specific or general time ofday for administration of the composition, or the indicia may be a dayindicia indicating a day of the week for administration of thecomposition.

The composition of the present invention may be used prior to and duringmenopause. Use of the compositions may commence at the onset ofmenopause. The composition of the present inventive subject matter ispreferably administered during a period commencing no later than theappearance of the first symptoms associated with menopause andcontinuing throughout a woman's life. More preferably, the compositionis administered during a period of time commencing just prior tomenopause or just prior to any symptoms of menopause. The phrases “justprior to menopause” and “prior to any symptoms of menopause” areintended herein to include commencement of administration ofcompositions approximately one month to five years prior to an agegenerally identified with initiation of menopause.

Preferably, the commencement of administration of the composition iswhen the woman is thirty five to fifty years of age. More preferably,the commencement of administration is one month prior to the womanturning forty years of age. Even more preferably, the commencement ofadministration is one year prior to the woman turning forty years ofage. Most preferably, the commencement of administration is five yearsprior to the woman turning forty years of age.

The present inventive subject matter includes a method for providingnutritional supplementation to a menopausal woman. The methods includeadministration of the present composition to women during a criticalperiod. The critical period of administration is the period commencingjust prior to menopause and continuing through the postmenopausal periodof a woman's life.

The method of the present inventive subject matter may prevent or atleast minimize fatty acid deficiency in menopausal women. The presentmethod may also be used to prevent or treat symptoms associated withmenopause. Further, the present method may inhibit the loss in bone masscommonly experienced by menopausal women. The present method may delayonset of menopause and/or reduce possibility of premature menopause.

The present methods may be carried out alone or in conjunction with atherapeutic therapy or regimen, without limitation. The therapeutictherapy or regimen may be for treating symptoms associated withmenopause or may be entirely unrelated to menopause. For example,without limitation, the present method may be incorporated as part ofhormonal or estrogen therapy, or in combination with dietarymanipulation.

The foregoing is considered as illustrative only of the principles ofthe inventive subject matter. Further, since numerous modifications andchanges will readily occur to those skilled in the art, it is notdesired to limit the inventive subject matter to the exact constructionand operation shown and described, and accordingly all suitablemodifications and equivalents may be resorted to, falling within thescope of the inventive subject matter.

The following examples are illustrative of preferred embodiments of theinventive subject matter and are not to be construed as limiting theinventive subject matter thereto. All percentages are based on thepercent by weight of the final delivery system or formulation preparedunless otherwise indicated and all totals equal 100% by weight.

EXAMPLES Example 1

The following formulations are used to prepare compositions foradministration to premenopausal and menopausal women:

Component Dose Units Vitamin A (Beta Carotene) 5,000 I.U. Vitamin D 400I.U. Vitamin E 400 I.U. Vitamin C 100 mg. Vitamin B1 20 mg. Vitamin B220 mg. Vitamin B6 25 mg. Vitamin B12 50 mcg. Vitamin B3 100 mg. FolicAcid 1.0 mg. Calcium Carbonate 1,200 mg. Copper 2 mg. Zinc 15 mg.Selenium 65 mcg. DHA/Linolenic/Linoleic Acid 50/25/25 mg.

It would be anticipated that upon administration of the abovecomposition, an average normal menopausal woman would be expected tohave reduced incidence of nutritional deficiency and reducedmenopausal-related symptoms or disorders when compared to an averagenormal menopausal woman following a conventional nutritional regimen.

Example 2

The following compositions are for administration to premenopausal womenand menopausal women in accordance with the regimen indicated below:

Regimen Component Dose First Morning Calcium Carbonate 350 mg Tablet(orange): B Complex 55 mg Second Morning Calcium Carbonate 350 mg Tablet(white): Vitamin A 3,000 IU Vitamin C 100 IU Vitamin D 400 IU Selenium65 mcg Zinc 15 mg Copper 2 mg Evening Tablet Calcium Carbonate 350 mg BComplex 110 mg Vitamin A 2,000 IU Folic Acid 1 mg Evening CapsuleVitamin E 400 IU DHA 50 mg Linolenic Acid 25 mg Linoleic Acid 25 mgCalcium Carbonate 150 mg

It would be anticipated that upon following the above regimen, anaverage normal menopausal woman would be expected to have reducedincidence of nutritional deficiency and reduced menopausal-relatedsymptoms or disorders when compared to an average normal menopausalwoman following a conventional nutritional regimen.

Example 3

A soft gelatin supplement in accordance with the compositions ofExamples 1 and 2 above, may be prepared, by first combining mineral oiland soybean oil in a first vessel and blending it to form a uniform oilmixture, heating the oil mixture to 45 degrees Celsius, and then addingpropylene glycol. In a second vessel preheated to 70 degrees Celsius,yellow beeswax and soybean oil are added and blended until a uniform waxmixture is formed. The wax mixture is cooled to 35 degrees Celsius andthen added to the oil mixture. To this combined oil and wax mixture,folic acid, vitamin B₆, iron, magnesium, and calcium are then added andblended together to form a uniform biologically active mixture. Themixture is then cooled to 30 degrees Celsius to form a viscousbiologically active core composition, after which time the compositionis ready for encapsulation in a soft gelatin shell.

A soft gelatin shell is prepared by heating purified water in a suitablevessel and then adding gelatin. This water gelatin mixture is mixeduntil the gelatin is fully dissolved, and then glycerin, preservatives,one or more flavors, and one or more colorants are added. This gelatinmixture is blended well and cooled. The shells are then filled with thecore composition and formed in accordance with soft gelatin techniquescommonly used and well known to persons of skill in the art.

Example 4

The following compositions are for administration to premenopausal womenand menopausal women in accordance with the regimen indicated below:

Regimen Component Dose First Morning Calcium Carbonate 350 mg Tablet(orange): B Complex 55 mg Second Morning Calcium Carbonate 350 mg Tablet(white): Vitamin A 3,000 IU Vitamin C 100 IU Vitamin D 400 IU Selenium65 mcg Zinc 15 mg Copper 2 mg Evening Tablet Calcium Carbonate 350 mg BComplex 110 mg Vitamin A 2,000 IU Folic Acid 1 mg Evening CapsuleVitamin E 400 IU DHA 50 mg Linolenic Acid 25 mg Linoleic Acid 25 mgCalcium Carbonate 150 mg Evening Tablet Alendronate 10 mg

It would be anticipated that upon following the above regimen, anaverage normal menopausal woman would be expected to have reducedincidence of nutritional deficiency and reduced menopausal-relatedsymptoms or disorders when compared to an average normal menopausalwoman following a conventional nutritional regimen.

Example 5

The following compositions are for administration to premenopausal womenand menopausal women in accordance with the regimen indicated below:

Regimen Component Dose First Morning Calcium Carbonate 350 mg Tablet(orange): B Complex 55 mg Second Morning Calcium Carbonate 350 mg Tablet(white): Vitamin A 3,000 IU Vitamin C 100 IU Vitamin D 400 IU Selenium65 mcg Zinc 15 mg Copper 2 mg Evening Tablet Calcium Carbonate 350 mg BComplex 110 mg Vitamin A 2,000 IU Folic Acid 1 mg Evening CapsuleVitamin E 400 IU DHA 50 mg Linolenic Acid 25 mg Linoleic Acid 25 mgCalcium Carbonate 150 mg Evening Tablet PREMPRO ™ conjugated estrogens2.5 mg progesterone 2.5 mg

It would be anticipated that upon following the above regimen, anaverage normal menopausal woman would be expected to have reducedincidence of nutritional deficiency and reduced menopausal-relatedsymptoms or disorders when compared to an average normal menopausalwoman following a conventional nutritional regimen.

The inventive subject matter being thus described, it will be apparentthat the same may be varied in many ways. Such variations are not to beregarded as a departure from the spirit and scope of the inventivesubject matter, and all such modifications are intended to be within thescope of the appended claims.

1. A method of administering a composition to a menopausal woman, themethod comprising: administering a first fatty acid compound selectedfrom the group consisting of a linoleic acid compound, a derivativethereof and a combination thereof in an amount of about 10 mg to about1,000 mg; a second fatty acid compound selected from the groupconsisting of a linolenic acid compound, a derivative thereof andcombinations thereof in an amount of about 10 mg to about 1,000 mg; athird fatty acid compound selected from the group consisting of adocosahexaenoic acid compound, an omega-3 fatty acid, an omega-2 fattyacid, a derivative thereof and a combination thereof in an amount ofabout 10 mg to about 1,000 mg; a calcium compound or derivative thereofin an amount of about 400 mg to about 2500 mg; a folic acid compound orderivative thereof in an amount of about 0.4 mg to about 5.0 mg; avitamin C compound or derivative thereof in an amount of about 25 mg toabout 500 mg; a vitamin E compound or derivative thereof in an amount ofabout 10 mg to about 500 mg; with the weight ratio of the sum of theamounts of said first and second fatty acid compounds to the amount ofsaid third fatty acid compound being about 1:0.5 to 1.5; and with theweight ratio of the sum of the amounts of said first, second and thirdfatty acid compounds to the amount of said calcium compound orderivative thereof is being about 1:0.4 to 50, and said derivativesselected from the group consisting of salts, esters, metabolites,extracts, and isolates.
 2. The method of claim 1, wherein saidcomposition additionally contains a non-nutritional active.
 3. Themethod of claim 2, wherein the non-nutritional active is selected fromthe group consisting of hormones, steroids, fiber, estrogens,progestins, sedative-hypnotics, barbiturates, benzodiazepines,antidepressants, tranquilizers, sedatives, aminobisphosphonates,osteoporotics, herbals, herbal derivatives, phyto-chemical derivatives,antiplatelets and combinations thereof, with said derivatives selectedfrom the group consisting of salts, esters, metabolites, extracts, andisolates.
 4. The method of claim 2, wherein the non-nutritional activeis a hormone, and with the hormone being present in said composition inan amount ranging from about 0.15 mg to about 11.25 mg.
 5. The method ofclaim 2, wherein the non-nutritional active is selected from the groupconsisting of medroxyprogesterone acetate, megestrol acetate, clonidine,norethindrone acetate, ethinyl estradiol, conjugated estrogen, naturalestrogen, synthetic estrogen, estradiol, progesterone, clomiphene,clomiphene citrate, zuclomiphene, zuclomiphene citrate, enclomiphene,enclomiphene citrate, calcitonin, aspirin, alendronate, etidronate,pamidronate, clodronate, tiludronate, residronate, ibandronate andcombinations thereof.
 6. The method of claim 2, wherein thenon-nutritional active is an osteoporotic, and with the osteoporoticbeing present in said composition in an amount ranging from about 2.5 mgto about 60 mg.
 7. The method of claim 1, wherein the compositionadditionally contains an amino acid compound or derivative thereof, withsaid derivatives selected from the group consisting of salts, esters,metabolites, extracts, and isolates.
 8. The method of claim 7, whereinthe amino acid compound is selected from the group consisting ofleucine, isoleucine, valine and combinations thereof.
 9. A method ofadministering a composition to a menopausal woman, the methodcomprising: administering a first fatty acid compound selected from thegroup consisting of a linoleic acid compound, a derivative thereof and acombination thereof in an amount of about 10 mg to about 1,000 mg; asecond fatty acid compound selected from the group consisting of alinolenic acid compound, a derivative thereof and combinations thereofin an amount of about 10 mg to about 1,000 mg; a third fatty acidcompound selected from the group consisting of a docosahexaenoic acidcompound, an omega-3 fatty acid, an omega-2 fatty acid, a derivativethereof and a combination thereof in an amount of about 10 mg to about1,000 mg; a calcium compound or derivative thereof in an amount of about400 mg to about 2500 mg; a folic acid compound or derivative thereof inan amount of about 0.4 mg to about 5.0 mg; a vitamin C compound orderivative thereof in an amount of about 25 mg to about 500 mg; avitamin E compound or derivative thereof in an amount of about 10 mg toabout 500 mg; a vitamin A compound or derivative thereof in an amount ofabout 2,500 IU to about 6,500 IU; with the weight ratio of the sum ofthe amounts of said first and second fatty acid compounds to the amountof said third fatty acid compound being about 1:0.5 to 1.5; and with theweight ratio of the sum of said first, second and third fatty acidcompounds to the amount of said calcium compound or derivative thereofbeing about 1:0.4 to 50 with said derivatives selected from the groupconsisting of salts, esters, metabolites, extracts, and isolates.
 10. Amethod of administering a composition to a menopausal woman, the methodcomprising: administering a first fatty acid compound selected from thegroup consisting of a linoleic acid compound, a derivative thereof and acombination thereof in an amount of about 10 mg to about 1,000 mg; asecond fatty acid compound selected from the group consisting of alinolenic acid compound, a derivative thereof and combinations thereofin an amount of about 10 mg to about 1,000 mg; a third fatty acidcompound selected from the group consisting of a docosahexaenoic acidcompound, an omega-3 fatty acid, an omega-2 fatty acid, a derivativethereof and a combination thereof in an amount of about 10 mg to about1,000 mg; a calcium compound or derivative thereof in an amount of about400 mg to about 2500 mg; a folic acid compound or derivative thereof inan amount of about 0.4 mg to about 5.0 mg; a vitamin C compound or esterderivative thereof in an amount of about 25 mg to about 500 mg; avitamin E compound or derivative thereof in an amount of about 10 mg toabout 500 mg; a vitamin B6 compound or derivative thereof in an amountof about 10 mg to about 50 mg; a vitamin B12 compound or derivativethereof in an amount of about 25 mcg to about 75 mcg; a vitamin Dcompound or derivative thereof in an amount of about 200 IU to about 625IU; with the weight ratio of the sum of the amounts of said first andsecond fatty acid compounds to the amount of said third fatty acidcompound being about 1:0.5 to 1.5; and with the weight ratio of the sumof the amounts of said first, second and third fatty acid compounds tothe amount of said calcium compound or derivative thereof being about1:0.4 to 50 with said derivatives selected from the group consisting ofsalts, esters, metabolites, extracts, and isolates.
 11. A method ofadministering a composition to a menopausal woman, the methodcomprising: administering a first fatty acid compound selected from thegroup consisting of a linoleic acid compound, a derivative thereof and acombination thereof in an amount of about 10 mg to about 1,000 mg; asecond fatty acid compound selected from the group consisting of alinolenic acid compound, a derivative thereof and combinations thereofin an amount of about 10 mg to about 1,000 mg; a third fatty acidcompound selected from the group consisting of a docosahexaenoic acidcompound, an omega-3 fatty acid, an omega-2 fatty acid, a derivativethereof and a combination thereof in an amount of about 10 mg to about1,000 mg; a calcium compound or derivative thereof in an amount of about400 mg to about 2500 mg; a folic acid compound or derivative thereof inan amount of about 0.4 mg to about 5.0 mg; a vitamin C compound orderivative thereof in an amount of about 25 mg to about 500 mg; avitamin E compound or derivative thereof in an amount of about 10 mg toabout 500 mg; and with the weight ratio of the sum of the amounts ofsaid first, second and third fatty acid compounds to the amount of saidcalcium compound or derivative thereof being about 1:0.4 to 50 with saidderivatives selected from the group consisting of salts, esters,metabolites, extracts, and isolates.
 12. The method of claim 11, whereinsaid composition additionally contains a non-nutritional active.
 13. Themethod of claim 12, wherein the non-nutritional active is selected fromthe group consisting of hormones, steroids, fiber, estrogens,progestins, sedative-hypnotics, barbiturates, benzodiazepines,antidepressants, tranquilizers, sedatives, aminobisphosphonates,osteoporotics, herbals, herbal derivatives, phyto-chemical derivatives,antiplatelets and combinations thereof.
 14. The method of claim 12,wherein the non-nutritional active is a hormone, and with the hormonebeing present in said composition in an amount ranging from about 0.15mg to about 11.25 mg.
 15. The method of claim 12, wherein thenon-nutritional active is selected from the group consisting ofmedroxyprogesterone acetate, megestrol acetate, clonidine, norethindroneacetate, ethinyl estradiol, conjugated estrogen, natural estrogen,synthetic estrogen, estradiol, progesterone, clomiphene, clomiphenecitrate, zuclomiphene, zuclomiphene citrate, enclomiphene, enclomiphenecitrate, calcitonin, aspirin, alendronate, etidronate, pamidronate,clodronate, tiludronate, residronate, ibandronate and combinationsthereof.
 16. The method of claim 12, wherein the non-nutritional activeis an osteoporotic, and with the osteoporotic being present in saidcomposition in an amount ranging from about 2.5 mg to about 60 mg. 17.The method of claim 11, wherein the composition additionally contains anamino acid compound or derivative thereof with said derivatives selectedfrom the group consisting of salts, esters, metabolites, extracts, andisolates.
 18. The method of claim 17, wherein the amino acid compound isselected from the group consisting of leucine, isoleucine, valine andcombinations thereof.